Effectiveness of pharmacological and non-pharmacological interventions for treatment-resistant depression in older patients: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>Depression in older adults is often undertreated. A 2011 systematic review of treatments for treatment-resistant depression (TRD) in older adults identified one placebo-controlled randomised controlled trial (RCT). We aimed to update this review, synthesising evidence for the effectiveness of treatments for TRD in older people.<h4>Methods</h4>We systematically searched electronic databases (PubMed, Cochrane, Web of Science) from 9 January 2011 through 10 December 2023 (updating our search on 7 January 2024 for RCTs investigating TRD therapies in adults aged ≥55 years, defining treatment resistance as ≥1 unsuccessful treatment. We assessed bias with the Cochrane Risk of Bias (RoB) 2 tool, meta-analysed remission rates and evaluated evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria.<h4>Results</h4>14 studies (11 newly identified, 3 from previous review) involving 1196 participants (mean age 65.0, male/female 548/648) met the inclusion criteria; 10 were placebo controlled and 4 were rated as low RoB. The pooled proportion of participants in intervention arms remitting was 0.35 (17 arms; 95% CI=0.26; 0.45). Relative to placebo, intervention participants were more likely to remit (9 studies; OR 2.42 (95% CI=1.49; 3.92)). Relative to controls, remission rates favoured ketamine (n=3; OR 2.91 (1.11; 7.65)), with a trend towards transcranial magnetic stimulation (TMS) (n=3; 1.99 (0.71; 5.61)), and in single placebo-controlled studies, selegiline, aripiprazole augmentation, pharmacogenetic-guided prescribing (PGP) and cognitive remediation favoured interventions.<h4>Conclusions</h4>We identified weak evidence that ketamine therapy and aripiprazole augmentation, and very weak evidence that TMS, PGP and cognitive remediation increased remission. Lack of evidence regarding routinely prescribed antidepressants and psychosocial treatments is problematic, requiring clinicians to extend evidence from younger populations.<h4>Prospero registration number</h4>CRD42023494513.

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